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Clinical Trial Details — Status: Active, not recruiting

Administrative data

NCT number NCT05387616
Other study ID # Alternative-C
Secondary ID 2018-004038-13
Status Active, not recruiting
Phase Phase 2
First received
Last updated
Start date October 19, 2020
Est. completion date May 19, 2026

Study information

Verified date March 2024
Source Ludwig-Maximilians - University of Munich
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The Alternative-C Trial is a prospective, multicenter Phase 2 Study to evaluate the efficacy of the chemotherapy-free combination of copanlisib and obinutuzumab in patients with previously untreated follicular lymphoma (FL) and a high tumor burden. Additionally, the combination should be evaluated in terms of secondary efficacy endpoints, treatment compliance, safety and patient-reported symptoms. The study Population includes Patients > 18 years of age with histologically confirmed follicular lymphoma grade 1, 2 or 3A with Ann Arbor Stage III/IV or stage II not suitable for radiotherapy and in need of therapy.


Recruitment information / eligibility

Status Active, not recruiting
Enrollment 98
Est. completion date May 19, 2026
Est. primary completion date September 16, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Subjects will only be included in the study, if they meet all of the following criteria: - Histologically confirmed follicular lymphoma grade 1, 2 or 3A with a biopsy performed within 12 months before study entry and with material available for central review and complementary scientific analyses - Ann Arbor stage III/IV, or stage II not suitable for radiotherapy, or stage II bulky disease - Age = 18 years - No prior lymphoma therapy - Need for start of therapy as defined by at least one of the following criteria: - bulky disease at study entry according to the GELF criteria (nodal or extranodal mass > 7 cm in its greatest diameter) - B symptoms (fever, drenching night sweats, or unintentional weight loss of > 10% of normal body weight over a period of 6 months or less) - hematopoietic insufficiency (granulocytopenia < 1500/µl, Hb < 10 g/dl, thrombocytopenia < 100000/µl) - compressive syndrome or high risk for compression syndrome - pleural/peritoneal effusion - symptomatic extranodal manifestations - At least one bi-dimensionally measurable lesion (> 2 cm in its largest dimension by CT scan or MRI) - Performance status = 2 on the ECOG scale - Adequate hematologic function (unless abnormalities are related to NHL), defined as follows: - Hemoglobin = 9.0 g/dL - Absolute neutrophil count = 1500/µl - Platelet count = 75000/µl - Women are not breast feeding, are using highly effective contraception (see section 11.4.1), are not pregnant, and agree not to become pregnant during participation in the study and during the 18 months thereafter (pregnancy testing is mandatory for premenopausal women). - Men agree not to father a child during participation in the study and during the 18 months thereafter. - Written informed consent Exclusion criteria: Subjects will not be included in the study if any of the following criteria apply: - Transformation to high-grade lymphoma (secondary to "low grade" FL) - Grade 3B follicular lymphoma - Presence or history of CNS disease (either CNS lymphoma or leptomeningeal lymphoma) - Known hypersensitivity to any of the study drugs - Known sensitivity to murine products - Patients with HbA1c > 8.5 % at Screening - Uncontrolled arterial hypertension despite optimal medical management (per investigator's assessment) - Regular use of corticosteroids during the last 4 weeks, unless administered at a dose equivalent to < 20 mg/day prednisone or administered as prephase treatment according to study protocol (see section 7.2 of study protocol) - Concomitant use of strong CYP3A4 inhibitors and/or inducers - Prior or concomitant malignancies except: - non-melanoma skin cancer or adequately treated in carcinoma in situ of the cervix - other malignant diseases not specified above which have been curatively treated by surgery alone and from which subject is disease-free for = 5 years without further treatment - Serious disease interfering with a regular therapy according to the study protocol: - Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification - pulmonary (e.g. chronic lung disease with hypoxemia) - endocrine (e.g. severe, not sufficiently controlled diabetes mellitus) - renal insufficiency (unless caused by the lymphoma): creatinine > 2x normal value and/or creatinine clearance < 50 ml/min) - impairment of liver function (unless caused by the lymphoma): transaminases > 3x normal or bilirubin > 2.0 mg/dl (unless caused by known Morbus Meulengracht [Gilbert-Meulengracht-Syndrome]) - Positive test results for chronic HBV infection (defined as positive HBsAg serology) Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) may be included if HBV DNA is undetectable, provided that they are willing to undergo monthly DNA testing. Patients who have protective titers of hepatitis B surface antibody (HBsAb) after vaccination or prior but cured hepatitis B are eligible. - Positive test results for hepatitis C (hepatitis C virus [HCV] antibody serology testing) Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA. - Clinically significant history of liver disease, including viral or other hepatitis, or cirrhosis - Known history of HIV seropositive status - Patients with a history of confirmed PML - Vaccination with a live vaccine within 28 days prior to registration - Recent major surgery (within 4 weeks prior to the start of Cycle 1) - History of stroke or intracranial hemorrhage within 6 months prior to registration - Serious underlying medical conditions, which could impair the ability of the patient to undergo the treatment offered in the study (e.g. ongoing infection, gastric ulcers, active autoimmune disease) - Treatment within another clinical study within 30 days prior to study entry - Prior organ, bone marrow, or peripheral blood stem cell transplantation - Known or persistent abuse of medication, drugs, or alcohol - Any other co-existing medical or psychological condition that will preclude participation in the study or compromise ability to give informed consent

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Copanlisib
Induction therapy will comprise 6 cycles of copanlisib, administered by intravenous Infusion at a dose of 60 mg on day 1,8,15 of cycles 1-6 to be given every 28 days. Consolidation therapy will comprise another 24 weeks of copanlisib in patients with clinical Remission 28 days after the last induction cycle. It will be administered by intravenous Infusion at a dose of 60 mg on days 1 and 15 of cycles 7 - 12 to be given every 28 days. Maintenance therapy will comprise another 72 weeks of copanlisib in patients with clinical remissions 28 days after the last consolidation cycle.
Obinutuzumab
Induction therapy will comprise 6 cycles of obinutuzumab, administered by intravenous infusion at a dose of 1000 mg on days 1,8, 15 of cycle 1 and on day 1 of cycles 2 - 6 to be given every 28 days. Consolidation therapy will comprise of another 24 weeks of obinutuzumab in patients with clinical remission 28 days after the last induction cycle. Obinutuzumab will be applied at a dose of 1000 mg by intravenous infusion every 8 weeks. Maintenance therapy will comprise another 72 weeks in patients with clinical remission 28 days after the last consolidation cycle. Obinutuzumab will be applied at a dose of 1000 mg by intravenous infusion every 8 weeks.

Locations

Country Name City State
Germany Gesundheitszentrum St. Marien GmbH Amberg
Germany HELIOS Klinikum Bad Saarow Bad Saarow
Germany Charité Campus Benjamin Franklin Berlin
Germany Vivantes Netzwerk für Gesundheit GmbH - Vivantes Klinikum am Urban Berlin
Germany Universitätsklinikum Bonn Bonn
Germany Klinikum Chemnitz gGmbH Chemnitz
Germany Carl-Thiem-Klinikum Cottbus gGmbH Cottbus
Germany Cancer Center Dachau Dachau
Germany Städtisches Klinikum Dessau Dessau
Germany Gemeinschaftspraxis Dr. med. J. Mohm und Dr. med. G. Prange-Krex Dresden
Germany Marien Hospital Düsseldorf Düsseldorf
Germany Universitätsklinikum Essen Essen
Germany Centrum für Hämatologie und Onkologie Bethanien Frankfurt am Main
Germany Universitätsklinikum Freiburg Freiburg
Germany Universitätsklinikum Heidelberg Heidelberg
Germany Universitätsklinikum Jena Jena
Germany Klinikum Kassel Kassel
Germany Universitätsklinikum Schleswig-Holstein Kiel
Germany Praxis für Hämatologie und Onkologie Koblenz
Germany Klinikum der Stadt Ludwigshafen gGmbH Ludwigshafen
Germany Schwerpunktpraxis für Hämatologie und Onkologie Magdeburg
Germany Universitätsklinikum Magdeburg A.ö.R. Magdeburg
Germany Universitätsklinik Mannheim Mannheim
Germany Kliniken Maria Hilf GmbH, Krankenhaus St. Franziskus Mönchengladbach
Germany Klinikum rechts der Isar der TU München München
Germany LMU Klinikum München Bavaria
Germany Gemeinschaftspraxis für Hämatologie und Onkologie Münster
Germany Universitätsklinikum Münster Münster
Germany Stauferklinikum Schwäbisch Gmünd Mutlangen
Germany Friedrich Ebert Krankenhaus Neumünster
Germany Rheinland Klinikum, Lukaskrankenhaus Neuss Neuss
Germany Brüderkrankenhaus St. Josef Paderborn Paderborn
Germany Klinikum Südstadt Rostock Rostock
Germany Universitätsmedizin Rostock Rostock
Germany Gemeinschaftspraxis Dr. med. G.A. Jacobs Saarbrücken
Germany Klinikum Mutterhaus der Borromäerinnen gGmbH Trier
Germany Universitätsklinikum Tübingen Tübingen
Germany Universitätsklinikum Ulm Ulm
Germany Petrus Kankenhaus Wuppertal
Germany Hämatologisch-Onkologische Schwerpunktpraxis Würzburg

Sponsors (3)

Lead Sponsor Collaborator
Ludwig-Maximilians - University of Munich Bayer, Roche Pharma AG

Country where clinical trial is conducted

Germany, 

Outcome

Type Measure Description Time frame Safety issue
Primary One-year progression-free survival (PFS) probability from study registration The rate of patients achieving a progression free survival of more than one year after registration (one-year PFS rate) will serve as early readout for efficacy. 1 year
Secondary Complete remission (CR) rates and overall response (CR or partial remission, PR) rates at end of induction (month 6), at end of consolidation (month 12), and at end of maintenance (month 30)
Secondary Progression free survival from registration continuous observation up to 78 months
Secondary Duration of response from end of induction to progression or death assessed up to 72 months
Secondary Cumulative incidence of progression from registration to end of study assessed up to 78 months
Secondary Failure-free survival event defined by failure to achieve a CR/PR after 6 months or progression after CR or PR or death from any cause from start of therapy assessed up to 78 months
Secondary Time to next anti-lymphoma therapy and time to next chemotherapy based treatment from start of first-line therapy up to 78 months
Secondary Overall survival from registration up to 78 months
Secondary Treatment associated adverse events continuous observation up to 78 months
Secondary Percentage of MRD-negative patients therapy (month 12), and at end maintenance therapy (month 30)
Secondary Duration of molecular remission for MRD negative patients from end of induction therapy up to 72 months
Secondary Cumulative incidence of secondary transformations to aggressive lymphoma ongoing observation up to 78 months
Secondary Cumulative incidence of secondary malignancies ongoing observation up to 78 months
Secondary Percentage of patients with compliance to therapy after 6, 12, and 30 months
Secondary Frequency of patient-reported lymphoma symptoms and concerns (FACT-Lym) Baseline, End of Induction, End of Consolidation, End of Maintenance, and every 6 months during FU for at least 2 years until end of the whole study
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